Hypertension is one of representative lifestyle-related diseases. Hypertension which is left untreated for long time lays a heavy burden on the cardiovascular system and results in arteriosclerosis to progress, thus causing various disorders in important organs, such as cerebral hemorrhage, cerebral infarction, cardiac failure, angina pectoris, myocardial infarction, renal failure and the like. Accordingly, the purpose of treating hypertension lies not only in lowering the blood pressure, but also in improving and/or preventing disorders in important organs including brain, heart and kidney, by controlling the blood pressure. As a method of treating hypertension, there are available fundamental treatments based on improvement in the lifestyle, such as dietetic therapy, exercise therapy and the like, as well as an attempt to control the blood pressure by positive pharmaceutical intervention.
The renin-angiotensin (RA) system is a system of biosynthesis of angiotensin II (AII), which is a major vasopressor factor, and takes an important role in the control of the blood pressure and the amount of body fluid. AII exhibits a strong vasoconstrictive effect brought by the intervention of AII receptors on the cellular membrane, thus raising the blood pressure, and also promotes cellular propagation or production of extracellular matrix by directly acting on the AII receptors in the cardiac cells or renal cells. Therefore, drugs inhibiting increase in the activity of the RA system can be expected to have a blood pressure lowering action as well as a powerful organ protecting action, and thus active researches on such drugs have been conducted so far.
The method of inhibiting the AII action is broadly classified into methods of inhibiting the biosynthesis of AII and methods of inhibiting the binding of AII to AII receptors. For the drugs inhibiting the biosynthesis of AII, angiotensin converting enzyme (ACE) inhibitory drugs have been already put to practical use and are being confirmed to have a blood pressure lowering action as well as an effect for protecting various organs. However, since ACE is an enzyme identical to kininase II, which is a bradykinin degrading enzyme, ACE inhibitory drug inhibits the biosynthesis of AII as well as the degradation of bradykinin. As a result, ACE inhibitory drugs are believed to induce side effects such as dry cough, angioedema and the like, which are considered to be caused by accumulation of bradykinin.
As the drugs inhibiting the binding of AII to AII receptors, AII type 1 receptor blockers (ARB) have been developed. ARB has a merit in that it can inhibit, at the receptor level, the action of AII that is biosynthesized by not only ACE but also an enzyme other than ACE, such as chymase and the like. It is known that administration of ACE inhibitors and ARB increases the plasma renin activity (PRA) as a compensatory feedback effect, since these drugs act on a more peripheral region of the RA system.
Renin is an enzyme occupying a position at the uppermost stream of the RA system, and converts angiotensinogen to angiotensin I. A renin inhibitory drug inhibits the RA system by inhibiting the biosynthesis of AII in the same manner as the ACE inhibitory drugs do, and thus can be expected to have a blood pressure lowering action or an effect of protecting various organs. Since the renin inhibitory drug does not have influence on the metabolism of bradykinin, it is believed to have no risk of side effects, such as dry cough and the like, that are observed with the ACE inhibitory drugs. Furthermore, while the ACE inhibitory drugs or ARB increase the PRA level, the renin inhibitory drugs are the only drugs that can reduce PRA.
As renin inhibitors, orally administrable Aliskiren has been reported (Chem. Biol., 2000, vol. 7, pages 493-504; Hypertension, 2003, vol. 42, pages 1137-1143; J. Hypertens., 2005, vol. 23, pages 417-426 etc.).
As other renin inhibitors, the following compounds have been reported.
(1) A compound represented by the formula
wherein G is any one of groups represented by the following formulas (a) to (c)
R1a is an optionally substituted C1-6 alkyl group, an optionally substituted C2-6 alkenyl group, an optionally substituted C2-6 alkynyl group, an optionally substituted C3-10 cycloalkyl group, an optionally substituted C5-6 cycloalkenyl group or an optionally substituted 5-membered to 10-membered monocyclic or polycyclic heteroaryl-C1-4 alkyl group;R1b, R1c, R1d and R1e are the same or different and each independently is a hydrogen atom, a halogen atom, a hydroxyl group, a formyl group, a carboxy group, a cyano group, an optionally substituted C1-6 alkyl group, an optionally substituted C2-6 alkenyl group, an optionally substituted C2-6 alkynyl group, an optionally substituted C3-10 cycloalkyl group, an optionally substituted C5-6 cycloalkenyl group, an optionally substituted C6-10 aryl group, an optionally substituted C7-14 aralkyl group, an optionally substituted 5-membered to 10-membered monocyclic or polycyclic heteroaryl group, an optionally substituted 5-membered to 10-membered monocyclic or polycyclic heteroaryl C1-4 alkyl group, an optionally substituted saturated heterocyclic group, an optionally substituted C1-6 alkylthio group, an optionally substituted C1-6 alkylsulfinyl group, an optionally substituted C1-6 alkylsulfonyl group, an optionally substituted C6-10 arylthio group, an optionally substituted C6-10 arylsulfinyl group, an optionally substituted C6-10 arylsulfonyl group, an optionally substituted C1-6 alkoxy group, an optionally substituted C3-6 alkynyloxy group, an optionally substituted C3-6 cycloalkyloxy group, an optionally substituted C6-10 aryloxy group, an optionally substituted C7-14 aralkyloxy group, an optionally substituted 5-membered to 10-membered monocyclic or polycyclic heteroaryloxy group, an optionally substituted 5-membered to 10-membered monocyclic or polycyclic heteroaryl C1-4 alkyloxy group, an optionally substituted amino group, an optionally substituted aminocarbonyl group, an optionally substituted aminocarbonyloxy group, an optionally substituted aminosulfonyl group, an optionally substituted C1-6 alkoxycarbonyl group, an optionally substituted C3-6 cycloalkyloxycarbonyl group, an optionally substituted C1-4 alkylcarbonyl group, an optionally substituted C3-6 cycloalkylcarbonyl group, an optionally substituted C6-10 arylcarbonyl group or an optionally substituted 5-membered to 10-membered monocyclic or polycyclic heteroarylcarbonyl group; R1f is a hydrogen atom, a halogen atom, a hydroxyl group, a cyano group, an optionally substituted C1-6 alkyl group, an optionally substituted C2-6 alkenyl group, an optionally substituted C2-6 alkynyl group, an optionally substituted C3-10 cycloalkyl group, an optionally substituted C5-6 cycloalkenyl group, an optionally substituted C6-10 aryl group, an optionally substituted C7-14 aralkyl group, an optionally substituted 5-membered to 10-membered monocyclic or polycyclic heteroaryl group, an optionally substituted 5-membered to 10-membered monocyclic or polycyclic heteroaryl C1-4 alkyl group, an optionally substituted saturated heterocyclic group, an optionally substituted C1-6 alkylthio group, an optionally substituted C1-6 alkylsulfinyl group, an optionally substituted C1-6 alkylsulfonyl group, an optionally substituted C1-6 alkoxy group, an optionally substituted C3-6 alkynyloxy group, an optionally substituted C3-6 cycloalkyloxy group, an optionally substituted C6-10 aryloxy group, an optionally substituted C7-14 aralkyloxy group, an optionally substituted 5-membered to 10-membered monocyclic or polycyclic heteroaryl C1-4 alkyloxy group, an optionally substituted amino group, an optionally substituted aminocarbonyl group, an optionally substituted aminosulfonyl group, an optionally substituted C1-4 alkoxycarbonyl group, an optionally substituted C3-6 cycloalkyloxycarbonyl group, an optionally substituted C1-4 alkylcarbonyl group, an optionally substituted C3-6 cycloalkylcarbonyl group, an optionally substituted C6-10 arylcarbonyl group or an optionally substituted 5-membered to 10-membered monocyclic or polycyclic heteroarylcarbonyl group; R2 is an optionally substituted C1-6 alkyl group, an optionally substituted C2-6 alkenyl group, an optionally substituted C2-6 alkynyl group, an optionally substituted C3-6 cycloalkyl group, an optionally substituted C5-6 cycloalkenyl group, an optionally substituted C6-10 aryl group, an optionally substituted C7-14 aralkyl group or an optionally substituted 5-membered to 10-membered monocyclic or polycyclic heteroaryl group;R3a, R3b, R3c and R3d are the same or different and each independently is a halogen atom, a cyano group or a group: -A-B (wherein A is a single bond, —(CH2)S0-, —(CH2)SN(R4)—, —(CH2)SSO2—, —(CH2)SCO—, —(CH2)SCOO—, —(CH2)SN(R4) CO—, —(CH2)SN(R4)SO2—, —(CH2)SN(R4)COO—, —(CH2)SOCON(R4)—(CH2)SO—CO—, —(CH2)SN(R4)—, —(CH2)SN(R4)CON(R4)— or —(CH2)SSO2N(R4)—, B is a hydrogen atom, an optionally substituted C1-6 alkyl group, an optionally substituted C2-6 alkenyl group, an optionally substituted C2-6 alkynyl group, an optionally substituted C3-6 cycloalkyl group, an optionally substituted C5-6 cycloalkenyl group, an optionally substituted C6-10 aryl group, an optionally substituted C7-14 aralkyl group, an optionally substituted 5-membered to 10-membered monocyclic or polycyclic heteroaryl group, an optionally substituted 5-membered to 10-membered monocyclic or polycyclic heteroaryl C1-4 alkyl group or an optionally substituted 5-membered or 6-membered saturated heterocyclic group (when A is —(CH2)SN(R4)—, —(CH2)SOCON(R4)—, —(CH2)SCON(R4)—, —(CH2)SN(R4)CON(R4)— or —(CH2)6SO2N(R4)—, R4 and B may be bonded to each other to form a ring)), or two of R3a, R3b, R3c and R3d are hydrogen atoms, and the other two are bonded to each other to form a bridged ring together with the hetero ring;R4 is a hydrogen atom, an optionally substituted C1-6 alkyl group, an optionally substituted C3-6 cycloalkyl group, an optionally substituted C6-10 aryl group, an optionally substituted C7-14 aralkyl group or an optionally substituted 5-membered to 10-membered monocyclic or polycyclic heteroaryl group;s is 0, 1 or 2 (when A is —(CH2)SN(R4)—, s is 0 or 2, and when A is —(CH2)SCON(R4)—, s is 1 or 2); andn is 0, 1 or 2, or a salt thereof (see WO2009/14217).(2) A compound represented by the formula
wherein R1a is an optionally substituted C1-6 alkyl group, an optionally substituted C2-10 alkenyl group, an optionally substituted C2-6 alkynyl group, an optionally substituted C3-6 cycloalkyl group, an optionally substituted C5-6 cycloalkenyl group, an optionally substituted C1-6 alkylsulfinyl group, an optionally substituted C1-6 alkylsulfonyl group, an optionally substituted aminocarbonyl group, an optionally substituted C1-4 alkoxycarbonyl group or an optionally substituted C1-4 alkylcarbonyl group;R1b and R1e are the same or different and each independently is a hydrogen atom, a halogen atom, a cyano group, an optionally substituted C1-6 alkyl group, an optionally substituted C1-6 alkoxy group, an optionally substituted C3-6 cycloalkyloxy group or an optionally substituted aminocarbonyl group;R1c and R1d are the same or different and each independently is a hydrogen atom, a halogen atom, a hydroxyl group, a formyl group, a carboxy group, a cyano group, an optionally substituted C1-6 alkyl group, an optionally substituted C2-6 alkenyl group, an optionally substituted C2-6 alkynyl group, an optionally substituted C3-10 cycloalkyl group, an optionally substituted C5-6 cycloalkenyl group, an optionally substituted C6-10 aryl group, an optionally substituted C7-14 aralkyl group, an optionally substituted 5-membered to 10-membered monocyclic or polycyclic heteroaryl group, an optionally substituted 5-membered to 10-membered monocyclic or polycyclic heteroaryl C1-4 alkyl group, an optionally substituted saturated heterocyclic group, an optionally substituted C1-6 alkylthio group, an optionally substituted C1-6 alkylsulfinyl group, an optionally substituted C1-6 alkylsulfonyl group, an optionally substituted C6-10 arylthio group, an optionally substituted C6-10 arylsulfinyl group, an optionally substituted C6-10 arylsulfonyl group, an optionally substituted C1-6 alkoxy group, an optionally substituted C3-6 alkynyloxy group, an optionally substituted C3-10 cycloalkyloxy group, an optionally substituted C6-10 aryloxy group, an optionally substituted C7-14 aralkyloxy group, an optionally substituted 5-membered to 10-membered monocyclic or polycyclic heteroaryloxy group, an optionally substituted 5-membered to 10-membered monocyclic or polycyclic heteroaryl C1-4 alkyloxy group, an optionally substituted amino group, an optionally substituted aminocarbonyl group, an optionally substituted aminosulfonyl group, an optionally substituted C1-4 alkoxycarbonyl group, an optionally substituted C3-6 cycloalkyloxycarbonyl group, an optionally substituted C1-4 alkylcarbonyl group, an optionally substituted C3-6 cycloalkylcarbonyl group, an optionally substituted C6-10 arylcarbonyl group or an optionally substituted 5-membered to 10-membered monocyclic or polycyclic heteroarylcarbonyl group; R1f are the same or different and each independently is a hydrogen atom, a halogen atom, a cyano group, an optionally substituted C1-6 alkyl group, an optionally substituted C1-6 alkoxy group, an optionally substituted C3-10 cycloalkyl group, an optionally substituted C2-6 alkenyl group, an optionally substituted C2-6 alkenyloxy group, an optionally substituted C3-6 alkynyl group, an optionally substituted C3-6 alkynyloxy group or an optionally substituted C3-10 cycloalkyloxy group;R2 is an optionally substituted C1-6 alkyl group, an optionally substituted C2-6 alkenyl group, an optionally substituted C2-6 alkynyl group, an optionally substituted C3-10 cycloalkyl group, an optionally substituted C5-6 cycloalkenyl group, an optionally substituted C6-10 aryl group, an optionally substituted C7-14 aralkyl group or an optionally substituted 5-membered to 10-membered monocyclic or polycyclic heteroaryl group;R3a, R3b, R3c and R3d are the same or different and each independently is a halogen atom, a cyano group or a group: -A-B (wherein A is a single bond, —(CH2)S0-, —(CH2)SN(R4)—, —(CH2)SSO2—, —(CH2)SCO—, —(CH2)SCOO—, —(CH2)SN(R4) CO—, —(CH2)SN(R4)SO2—, —(CH2)SN(R4)COO—, —(CH2)SOCON(R4)—, —(CH2)SO—CO—, —(CH2)SON(R4)—, —(CH2)SN(R4)CON(R4)— or —(CH2)SSO2N(R4)—,B is a hydrogen atom, an optionally substituted C1-6 alkyl group, an optionally substituted C2-6 alkenyl group, an optionally substituted C2-6 alkynyl group, an optionally substituted C3-6 cycloalkyl group, an optionally substituted C5-6 cycloalkenyl group, an optionally substituted C6-10 aryl group, an optionally substituted C7-14 aralkyl group, an optionally substituted 5-membered to 10-membered monocyclic or polycyclic heteroaryl group, an optionally substituted 5-membered to 10-membered monocyclic or polycyclic heteroaryl C1-4 alkyl group or an optionally substituted saturated heterocyclic group (when A is —(CH2)SN(R4)—, —(CH2)SOCON(R4)—, —(CH2)SCON(R4)—, —(CH2)SN(R4)CON(R4)— or —(CH2)SSO2N(R4)—, R4 and B may be bonded to each other to form a ring)), or two of R3a, R3b, R3c and R3d are hydrogen atoms, and the other two are bonded to each other to form a bridged ring together with the hetero ring;R4 is a hydrogen atom, an optionally substituted C1-6 alkyl group, an optionally substituted C3-6 cycloalkyl group, an optionally substituted C6-10 aryl group, an optionally substituted C7-14 aralkyl group or an optionally substituted 5-membered to 10-membered monocyclic or a polycyclic heteroaryl group;s is 0, 1 or 2 (when A is —(CH2)SN(R4)—, s is 0 or 2, and when A is —(CH2)SCON(R4)—, s is 1 or 2); andn is 0, 1 or 2, or a salt thereof (see WO2009/05002).(3) A compound represented by the formula
wherein
R1 is a substituent;
R2 is a cyclic group optionally having substituent(s), a C1-10 alkyl optionally having substituent(s), a C2-10 alkenyl optionally having substituent(s) or a C2-10 alkynyl optionally having substituent(s);
R3 is a hydrogen atom, a halogen atom, a C1-6 alkyl or C1-6 alkoxy;
ring A is a nitrogen-containing heterocycle optionally having substituent(s); and
ring B is a piperazine optionally further having substituent(s) besides R1, or a salt thereof (see WO2009/001915).
(4) A compound represented by the formula
wherein R1 is A) an alkyl group substituted by the group selected from 1) an optionally substituted alkoxy group, 2) a hydroxyl group, 3) a halogen atom, 4) an optionally substituted aryl group, 5) an optionally substituted tetrahydronaphthyl group, 6) an optionally substituted indolyl group, 7) an optionally substituted benzofuranyl group, 8) an optionally substituted benzothienyl group, 9) an optionally substituted quinolyl group, 10) an optionally substituted dihydrochromenyl group, 11) an optionally substituted dihydrobenzofuranyl group, 12) an optionally substituted indazolyl group, 13) an optionally substituted pyrrolopyridinyl group, 14) an optionally substituted benzoxazinyl group, 15) an optionally substituted xanthenyl group, 16) an optionally substituted indolinyl group and 17) an optionally substituted imidazopyridinyl group, B) an optionally substituted aryl group, C) an optionally substituted heterocyclic group, D) a cycloalkyl group or E) an alkyl group,R2 is A) an alkyl group substituted by the group selected from 1) an optionally substituted alkoxy group, 2) a hydroxyl group, 3) a halogen atom, 4) an optionally substituted aryl group, 5) an optionally substituted tetrahydronaphthyl group, 6) an optionally substituted indolyl group, 7) an optionally substituted benzofuranyl group, 8) an optionally substituted benzothienyl group, 9) an optionally substituted quinolyl group, 10) an optionally substituted dihydrochromenyl group, 11) an optionally substituted dihydrobenzofuranyl group, 12) an optionally substituted indazolyl group, 13) an optionally substituted pyrrolopyridinyl group, 14) an optionally substituted benzoxazinyl group, 15) an optionally substituted xanthenyl group, 16) an optionally substituted indolinyl group and 17) an optionally substituted imidazopyridinyl group, B) an optionally substituted aryl group, C) an optionally substituted heterocyclic group, D) an optionally substituted alkylcarbonyl group, E) an optionally substituted arylcarbonyl group, F) an optionally substituted heterocyclic group-substituted carbonyl group or G) a cycloalkylcarbonyl group, T is a methylene group or a carbonyl group, andR3, R4, R5 and R6 are the same or different and each is a hydrogen atom, an optionally substituted carbamoyl group or an optionally a substituted alkyl group, or a salt thereof (see WO2008/153182).(5) A compound represented by the formula
wherein R1a is an optionally substituted C1-6 alkyl group, a C3-6 cycloalkyl group substituted by C1-4 alkoxy, an optionally substituted C2-6 alkenyl group, an optionally substituted C2-6 alkenyloxy group, an optionally substituted C3-6 alkynyl group, an optionally substituted C3-6 alkynyloxy group, an optionally substituted C1-6 alkylsulfinyl group, an optionally substituted C1-6 alkylsulfonyl group, an optionally substituted C1-6 alkoxy group, an optionally substituted amino group, an optionally substituted aminocarbonyl group, an optionally substituted C1-4 alkoxycarbonyl group or an optionally substituted C1-4 alkylcarbonyl group;R1b and R1e are each a hydrogen atom, a halogen atom, a cyano group, an optionally substituted C1-6 alkyl group, an optionally substituted C1-6 alkoxy group, an optionally substituted C3-6 cycloalkyloxy group or an optionally substituted aminocarbonyl group;R1c and R1d are the same or different and each independently is a hydrogen atom, a halogen atom, a hydroxyl group, a formyl group, a carboxy group, a cyano group, an optionally substituted C1-6 alkyl group, an optionally substituted C2-6 alkenyl group, an optionally substituted C2-6 alkynyl group, an optionally substituted C3-10 cycloalkyl group, an optionally substituted C5-6 cycloalkenyl group, an optionally substituted C6-10 aryl group, an optionally substituted C7-14 aralkyl group, an optionally substituted 5-membered to 10-membered monocyclic or polycyclic heteroaryl group, an optionally substituted 5-membered to 10-membered monocyclic or polycyclic heteroaryl C1-4 alkyl group, an optionally substituted saturated heterocyclic group, an optionally substituted C1-6 alkylthio group, an optionally substituted C1-6 alkylsulfinyl group, an optionally substituted C1-6 alkylsulfonyl group, an optionally substituted C6-10 arylthio group, an optionally substituted C6-10 arylsulfinyl group, an optionally substituted C6-10 arylsulfonyl group, an optionally substituted C1-6 alkoxy group, an optionally substituted C3-6 alkynyloxy group, an optionally substituted C3-10 cycloalkyloxy group, an optionally substituted C6-10 aryloxy group, an optionally substituted C7-14 aralkyloxy group, an optionally substituted 5-membered to 10-membered monocyclic or polycyclic heteroaryloxy group, an optionally substituted 5-membered to 10-membered monocyclic or polycyclic heteroaryl C1-4 alkyloxy group, an optionally substituted amino group, an optionally substituted aminocarbonyl group, an optionally substituted aminosulfonyl group, an optionally substituted C1-4 alkoxycarbonyl group, an optionally substituted C3-10 cycloalkyloxycarbonyl group, an optionally substituted C1-4 alkylcarbonyl group, an optionally substituted C3-10 cycloalkylcarbonyl group, an optionally substituted C6-10 arylcarbonyl group or an optionally substituted 5-membered to 10-membered monocyclic or polycyclic heteroarylcarbonyl group; R1f and R1g are the same or different and each independently is a hydrogen atom, a halogen atom, a cyano group, an optionally substituted C1-6 alkyl group, an optionally substituted C1-6 alkoxy group, an optionally substituted C3-10 cycloalkyl group, an optionally substituted C2-6 alkenyl group, an optionally substituted C2-6 alkenyloxy group, an optionally substituted C3-6 alkynyl group, an optionally substituted C3-6 alkynyloxy group or an optionally substituted C3-10 cycloalkyloxy group;R2 is an optionally substituted C1-6 alkyl group, an optionally substituted C2-6 alkenyl group, an optionally substituted C2-6 alkynyl group, an optionally substituted C3-10 cycloalkyl group, an optionally substituted C5-6 cycloalkenyl group, an optionally substituted C6-10 aryl group, an optionally substituted C7-14 aralkyl group or an optionally substituted 5-membered to 10-membered monocyclic or polycyclic heteroaryl group;R3a, R3b, R3c and R3d are the same or different and each independently is a halogen atom, a cyano group or a group: -A-B (wherein A is a single bond, —(CH2)S0-, —(CH2)SN(R4)—, —(CH2)SSO2—, —(CH2)SCO—, —(CH2)SCOO—, —(CH2)SN(R4) CO—, —(CH2)SN(R4)SO2—, —(CH2)SN(R4)COO—, —(CH2)SOCON(R4)—, —(CH2)SO—CO—, —(CH2)SON(R4), —(CH2)SN(R4)CON(R4)— or —(CH2)SSO2N(R4)—,B is a hydrogen atom, an optionally substituted C1-6 alkyl group, an optionally substituted C2-6 alkenyl group, an optionally substituted C2-6 alkynyl group, an optionally substituted C3-6 cycloalkyl group, an optionally substituted C5-6 cycloalkenyl group, an optionally substituted C6-10 aryl group, an optionally substituted C7-14 aralkyl group, an optionally substituted 5-membered to 10-membered monocyclic or polycyclic heteroaryl group, an optionally substituted 5-membered to 10-membered monocyclic or polycyclic heteroaryl C1-4 alkyl group or an optionally substituted saturated heterocyclic group (when A is —(CH2)SN(R4)—, —(CH2)SOCON(R4)—, —(CH2)SCON(R4)—, —(CH2)SN(R4)CON(R4)— or —(CH2)SSO2N(R4)—, R4 and B may be bonded to each other to form a ring)), or two of R3a, R3b, R3c and R3d are hydrogen atoms, and the other two are bonded to each other to form a bridged ring together with the hetero ring;R4 is a hydrogen atom, an optionally substituted C1-6 alkyl group, an optionally substituted C3-6 cycloalkyl group, an optionally substituted C6-10 aryl group, an optionally substituted C7-14 aralkyl group or an optionally substituted 5-membered to 10-membered monocyclic or a polycyclic heteroaryl group;s is 0, 1 or 2 (when A is —(CH2)SN(R4)—, s is 0 or 2, and when A is —(CH2)SCON(R4)—, s is 1 or 2); andn is 0, 1 or 2, or a salt thereof (see WO2008/153135).(6) A compound represented by the formula
whereinR1 is a substituent,R2 is a cyclic group optionally having substituent(s), C1-10 alkyl optionally having substituent(s), C2-10 alkenyl optionally is having substituent(s) or C2-10 alkynyl optionally having substituent(s),R3 is a hydrogen atom, a halogen atom, C1-6 alkyl or C1-6 alkoxy,X is a bond or a spacer having 1 to 6 atoms in the main chain, ring A is a C5-7 cycloalkane optionally having substituent(s), andring B is a piperazine optionally further having substituent(s) besides R1, or a salt thereof (see WO2008/139941).(7) A compound represented by the formula
wherein R1 and R2 are each a hydrocarbon group optionally having substituent(s) or a heterocyclic group optionally having substituent(s), orR1 and R2 may form, together with the nitrogen atom bonded thereto, a nitrogen-containing heterocycle optionally having substituent(s),R3 is a substituent,ring A is a homocycle optionally having substituent(s) or a heterocycle optionally having substituent(s), or a salt thereof (see WO2009/051112).(8) A compound represented by the formula
wherein G is one group selected from the group consisting of the following formulas (a) to (d)

wherein R1a is an optionally substituted C1-6 alkyl group, a C3-6 cycloalkoxy group substituted by C1-4 alkoxy, an optionally substituted C2-6 alkenyl group, an optionally substituted C2-6 alkenyloxy group, an optionally substituted C3-6 alkynyl group, an optionally substituted C3-6 alkynyloxy group, an optionally substituted C1-6 alkylsulfinyl group, an optionally substituted C1-6 alkylsulfonyl group, an optionally substituted C1-6 alkoxy group, an optionally substituted amino group, an optionally substituted aminocarbonyl group, an optionally substituted C1-4 alkoxycarbonyl group or an optionally substituted C1-4 alkylcarbonyl group;
R1b and R1e are the same or different and each independently is a hydrogen atom, a cyano group, an optionally substituted C1-8 alkyl group, an optionally substituted C1-6 alkoxy group, an optionally substituted C2-6 alkenyl group, C1-6 alkylsulfonyl group, or a halogen atom;R1c and R1d are the same or different and each independently is a hydrogen atom, a halogen atom, a hydroxyl group, a formyl group, a carboxy group, a cyano group, an optionally substituted C1-6 alkyl group, an optionally substituted C2-6 alkenyl group, an optionally substituted C2-6 alkynyl group, an optionally substituted C3-10 cycloalkyl group, an optionally substituted C5-6 cycloalkenyl group, an optionally substituted C6-10 aryl group, an optionally substituted C7-14 aralkyl group, an optionally substituted 5-membered to 10-membered monocyclic or polycyclic heteroaryl group, an optionally substituted 5-membered or 6-membered saturated heterocyclic group, an optionally substituted C1-6 alkylthio group, an optionally substituted C1-6 alkylsulfinyl group, an optionally substituted C1-6 alkylsulfonyl group, an optionally substituted C6-10 arylthio group, an optionally substituted C6-10 arylsulfinyl group, an optionally substituted C6-10 arylsulfonyl group, an optionally substituted C1-6 alkoxy group, an optionally substituted C3-6 alkynyloxy group, an optionally substituted C3-10 cycloalkyloxy group, an optionally substituted C6-10 aryloxy group, an optionally substituted C7-14 aralkyloxy group, an optionally substituted 5-membered to 10-membered monocyclic or polycyclic heteroaryloxy group, an optionally substituted amino group, an optionally substituted aminocarbonyl group, an optionally substituted aminosulfonyl group, an optionally substituted C1-4 alkoxycarbonyl group, an optionally substituted C3-10 cycloalkyloxycarbonyl group, an optionally substituted C1-4 alkylcarbonyl group, an optionally substituted C3-10 cycloalkylcarbonyl group, an optionally substituted C6-10 arylcarbonyl group or an optionally substituted 5-membered to 10-membered monocyclic or polycyclic heteroarylcarbonyl group;R1f is a hydrogen atom, a halogen atom, a cyano group, an optionally substituted C3-6 cycloalkyl group, an optionally substituted C2-6 alkenyl group, an optionally substituted C2-6 alkenyloxy group, an optionally substituted C3-6 alkynyl group, an optionally substituted C3-6 alkynyloxy group, an optionally substituted C3-10 cycloalkyloxy group, an optionally substituted C1-6 alkoxy group or an optionally substituted C1-6 alkyl group;R2 is an optionally substituted C1-6 alkyl group, an optionally substituted C2-6 alkenyl group, an optionally substituted C2-6 alkynyl group, an optionally substituted C3-10 cycloalkyl group, an optionally substituted C5-6 cycloalkenyl group, an optionally substituted C6-10 aryl group, an optionally substituted C7-14 aralkyl group or an optionally substituted 5-membered to 10-membered monocyclic or polycyclic heteroaryl group;R3a, R3b, R3c and R3d are the same or different and each independently is a halogen atom, a hydroxyl group, a formyl group, a carboxy group, a cyano group or a group: -A-B (wherein A is a single bond, —(CH2)S0-, —(CH2)SN(R4)—, —(CH2)SSO2—, —(CH2)SCO—, —(CH2)SCOO—, —(CH2)SN(R4)CO—, —(CH2)SN(R4)SO2—, —(CH2)SN(R4)COO—, —(CH2)SOCON(R4)—, —(CH2)SO—CO—, —(CH2)SON(R4)—, —(CH2)SN(R4)CON(R4)— or —(CH2)SSO2N(R4)—,B is a hydrogen atom, an optionally substituted C1-6 alkyl group, an optionally substituted C2-6 alkenyl group, an optionally substituted C2-6 alkynyl group, an optionally substituted C3-10 cycloalkyl group, an optionally substituted C5-6 cycloalkenyl group, an optionally substituted C6-10 aryl group, an optionally substituted C7-14 aralkyl group, an optionally substituted 5-membered to 10-membered monocyclic or polycyclic heteroaryl group, an optionally substituted 5-membered to 10-membered monocyclic or polycyclic heteroaryl C1-4 alkyl group or an optionally substituted 5-membered or 6-membered saturated heterocyclic group (when A is —(CH2)SN(R4)—, —(CH2)SOCON(R4)—, —(CH2)SCON(R4)—, —(CH2)SN(R4)CON(R4)— or —(CH2)SSO2N(R4)—, R4 and B may be bonded to each other to form a ring)), or two of R3a, R3b, R3c and R3d are hydrogen atoms, and the other two are bonded to each other to form a bridged ring together with the hetero ring; R4 is a hydrogen atom, an optionally substituted C1-6 alkyl group, an optionally substituted C3-6 cycloalkyl group, an optionally substituted C6-10 aryl group, an optionally substituted C7-14 aralkyl group or an optionally substituted 5-membered to 10-membered monocyclic or polycyclic heteroaryl group;s is 0, 1 or 2 (when A is —(CH2)SN(R4)—, s is 0 or 2, andwhen A is —(CH2)SCON(R4)—, s is 1 or 2); andn is 0, 1 or 2, or a salt thereof (see WO 2008/136457).(9) A compound represented by the formula
wherein R1a is a hydrogen atom, a halogen atom, a hydroxyl group, a formyl group, a carboxy group, a cyano group, an optionally substituted C1-6 alkyl group, an optionally substituted C2-6 alkenyl group, an optionally substituted C2-6 alkynyl group, an optionally substituted C3-6 cycloalkyl group, a C1-6 alkylthio group, a C1-6 alkylsulfonyl group, a C1-6 alkoxy group optionally substituted by a halogen atom, C1-4 alkoxy or C3-6 cycloalkyl, an optionally substituted C3-6 cycloalkoxy group, an optionally substituted amino group, aminocarbonyl group, C1-4 alkoxycarbonyl group, a C1-4 alkylcarbonyl group, an optionally substituted C6-10 aryl group, an optionally substituted C6-10 aryloxy group or an optionally substituted C7-14 aralkyloxy group;
R1b is a C1-6 alkyl group substituted by mono-C1-6 alkoxycarbonylamino, an optionally substituted C1-6 alkylsulfinyl group, an optionally substituted C1-6 alkylsulfonyl group, a substituted C1-6 alkoxy group, an optionally substituted amino group, an optionally substituted aminocarbonyl group, an optionally substituted C1-4 alkoxycarbonyl group or an optionally substituted C1-4 alkylcarbonyl group (wherein the substituted C1-6 alkoxy group is substituted by one group selected from the group consisting of hydroxy, C1-4 alkoxy, C3-6 cycloalkoxy, trifluoromethyl, trifluoromethoxy, difluoromethoxy, carboxy, mono-C1-6 alkylcarbonylamino and mono-C1-6 alkoxycarbonylamino), R1c is a hydrogen atom, a halogen atom, a hydroxyl group, a formyl group, a carboxy group, a cyano group, an optionally substituted C1-6 alkyl group, an optionally substituted C3-6 cycloalkyl group, an optionally substituted C5-6 cycloalkenyl group, an optionally substituted 5-membered or 6-membered saturated heterocyclic group, an optionally substituted C1-6 alkylthio group, an optionally substituted C1-6 alkylsulfinyl group, an optionally substituted C1-6 alkylsulfonyl group, an optionally substituted C6-10 arylthio group, an optionally substituted C6-10 arylsulfinyl group, an optionally substituted C6-10 arylsulfonyl group, an optionally substituted C1-6 alkoxy group, an optionally substituted C3-6 cycloalkyloxy group, an optionally substituted C6-10 aryloxy group, an optionally substituted C7-14 aralkyloxy group, an optionally substituted amino group, an optionally substituted aminocarbonyl group, an optionally substituted C1-4 alkoxycarbonyl group, an optionally substituted C3-6 cycloalkyloxycarbonyl group, an optionally substituted C1-4 alkylcarbonyl group, an optionally substituted C3-6 cycloalkylcarbonyl group, an optionally substituted C6-10 arylcarbonyl group, an optionally substituted C7-14 aralkyl group or an optionally substituted 5-membered to 10-membered monocyclic or polycyclic heteroarylcarbonyl group, or R1a is a hydrogen atom; R1b and R1c in combination form a fused ring together with the hetero ring, which contains at least one hetero atom;
R2 is a hydrogen atom, an optionally substituted C1-6 alkyl group, an optionally substituted C2-6 alkenyl group, an optionally substituted C2-6 alkynyl group, an optionally substituted C3-10 cycloalkyl group, an optionally substituted C5-6 cycloalkenyl group, an optionally substituted C1-10 aryl group, an optionally substituted C7-14 aralkyl group or an optionally substituted 5-membered to 10-membered monocyclic or polycyclic heteroaryl group (when R1a is a C1-6 alkoxy group substituted by a halogen atom, R2 is not a hydrogen atom);R3a, R3b, R3c and R3d are the same or different and each independently is a halogen atom, a cyano group or a group: -A-B (wherein A is a single bond, —(CH2)SO—, —(CH2)SN(R4)—, —(CH2)SSO2—, —(CH2)SCO—, —(CH2)SCOO—, —(CH2)SN(R4) CO—, —(CH2)SN(R4)SO2—, —(CH2)SN(R4)COO—, —(CH2)SOCON(R4)—, —(CH2)SO—CO—, —(CH2)SCON(R4)—, —(CH2)SN(R4)CON(R4)— or —(CH2)SSO2N(R4)—,B is a hydrogen atom, an optionally substituted C1-6 alkyl group, an optionally substituted C2-6 alkenyl group, an optionally substituted C2-6 alkynyl group, an optionally substituted C3-10 cycloalkyl group, an optionally substituted C5-6 cycloalkenyl group, an optionally substituted C6-10 aryl group, an optionally substituted C7-14 aralkyl group, an optionally substituted 5-membered to 10-membered monocyclic or polycyclic heteroaryl group, an optionally substituted 5-membered to 10-membered monocyclic or polycyclic heteroaryl C1-4 alkyl group or an optionally substituted saturated heterocyclic group (when A is —(CH2)SN(R4)—, —(CH2)SOCON(R4)—, —(CH2)SCON(R4)—, —(CH2)SN(R4)CON(R4)— or —(CH2)SSO2N(R4)—, R4 and B may be bonded to each other to form a ring)), or two of R3a, R3b, R3c and R3d are hydrogen atoms, and the other two are bonded to each other to form a bridged ring together with the hetero ring;R4 is a hydrogen atom, optionally substituted C1-6 alkyl group, an optionally substituted C3-10 cycloalkyl group, an optionally substituted C6-10 aryl group, an optionally substituted C7-14 aralkyl group or an optionally substituted 5-membered to 10-membered monocyclic or polycyclic heteroaryl group;s is 0, 1 or 2 (when A is —(CH2)SN(R4)—, s is 0 or 2, and when A is —(CH2)SCON(R4)—, s is 1 or 2); andn is 0, 1 or 2, or a salt thereof (see WO2008/093737).(10) A compound represented by the formula
wherein R1 is hydrogen, unsubstituted or substituted alkyl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, unsubstituted or substituted aryl, unsubstituted or substituted heterocyclyl or unsubstituted or substituted cycloalkyl;R2 is unsubstituted or substituted alkyl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, unsubstituted or substituted aryl, unsubstituted or substituted heterocyclyl, unsubstituted or substituted cycloalkyl, or acyl;R3 is hydrogen, unsubstituted or substituted aryl or unsubstituted or substituted alkyl;R4 is unsubstituted or substituted alkyl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, unsubstituted or substituted aryl, unsubstituted or substituted heterocyclyl, unsubstituted or substituted cycloalkyl, or acyl;or R3 and R4 may form together a 3 to 7 membered nitrogen containing saturated hydrocarbon ring which can be unsubstituted or substituted;R6 is hydrogen, halo, unsubstituted alkyl or unsubstituted alkoxy;R7 and R8 are independently of each other hydrogen or halo; andT is methylene or carbonyl; or a salt thereof (see WO2007/077005).(11) A compound represented by the formula
wherein R1 is hydrogen, unsubstituted or substituted alkyl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, unsubstituted or substituted aryl, unsubstituted or substituted heterocyclyl or unsubstituted or substituted cycloalkyl;R2 is unsubstituted or substituted alkyl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, unsubstituted or substituted aryl, unsubstituted or substituted heterocyclyl, unsubstituted or substituted cycloalkyl, or acyl;R3 is hydrogen, unsubstituted or substituted aryl or unsubstituted or substituted alkyl,R4 is unsubstituted or substituted alkyl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, unsubstituted or substituted aryl, unsubstituted or substituted heterocyclyl, unsubstituted or substituted cycloalkyl, or acyl;or R3 and R4 may form together a 3 to 7 membered nitrogen containing saturated hydrocarbon ring which can be unsubstituted or substituted; andT is methylene or carbonyl; or a salt thereof (see WO2007/006534).(12) A compound represented by the formula
whereinring A is a 5- or 6-membered aromatic heterocycle optionally having substituent(s);U, V and W are each independently C or N, provided that when any one of U, V and W is N, then the others should be C;Ra and Rb are each independently a cyclic group optionally having substituent(s), a C1-10 alkyl group optionally having substituent(s), a C2-10 alkenyl group optionally having substituent(s), or a C2-10 alkynyl group optionally having substituent(s);X is a bond, or a spacer having 1 to 6 atoms in the main chain;Y is a spacer having 1 to 6 atoms in the main chain;Rc is a hydrocarbon group optionally containing heteroatom(s) as the constituting atom(s), which optionally has substituent(s);m and n are each independently 1 or 2; andring B optionally further has substituent(s), or a salt thereof (see WO2007/094513).
On the other hand, as heterocyclic compounds, the following compounds have been reported.
(13) In WO2007/111227, for example, a compound having the following formula is reported as a CCR4 inhibitor.
(14) In WO2006/101780, for example, a compound having the following formula is reported as a kinesin inhibitor.
(15) In WO2005/047251, for example, a compound having the following formula is reported as a melanocortin receptor agonist.
(16) In WO2005/019206, for example, a compound having the following formula is reported as a kinesin inhibitor.
(17) In WO2005/018547, for example, a compound having the following formula is reported as a kinesin inhibitor.
(18) In WO2004/037171, for example, a compound having the following formula is reported as a kinesin inhibitor.
(19) In WO2003/079973, for example, a compound having the following formula is reported as a kinesin inhibitor.
(20) In WO2003/037274, for example, a compound having the following formula is reported as a Na+ channel inhibitor.
(21) In WO97/09308, for example, a compound having the following formula is reported as a NPY receptor antagonist.
(22) In WO2003/000677, for example, a compound having the following formula is reported as an ORL-1 receptor ligand.

However, these reports do not describe a renin inhibitory activity.